scholarly journals Bypassing Pathogen‐Induced Inflammasome Activation for the Regulation of Interleukin‐1β Production by the Fungal PathogenCandida albicans

2009 ◽  
Vol 199 (7) ◽  
pp. 1087-1096 ◽  
Author(s):  
Frank L. van de Veerdonk ◽  
Leo A. B. Joosten ◽  
Isabel Devesa ◽  
Héctor M. Mora‐Montes ◽  
Thirumala‐Devi Kanneganti ◽  
...  
Keyword(s):  
Interleukin 1Β ◽  
Inflammasome Activation

scholarly journals Hepatic inflammasome activation as origin of Interleukin-1α and Interleukin-1β in liver cirrhosis

Gut ◽  
2020 ◽  
pp. gutjnl-2020-322621
Author(s):  
Michael Praktiknjo ◽  
Robert Schierwagen ◽  
Sofia Monteiro ◽  
Cristina Ortiz ◽  
Frank Erhard Uschner ◽  
...  
Keyword(s):  
Liver Cirrhosis ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Interleukin 1Α

scholarly journals Aberrant Expression of Interleukin-1β and Inflammasome Activation in Human Malignant Gliomas

PLoS ONE ◽  
2014 ◽  
Vol 9 (7) ◽  
pp. e103432 ◽  
Author(s):  
Leonid Tarassishin ◽  
Diana Casper ◽  
Sunhee C. Lee
Keyword(s):  
Malignant Gliomas ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Aberrant Expression

scholarly journals Candida albicans Morphogenesis Is Not Required for Macrophage Interleukin 1β Production

mBio ◽  
2012 ◽  
Vol 4 (1) ◽  
Author(s):  
Melanie Wellington ◽  
Kristy Koselny ◽  
Damian J. Krysan
Keyword(s):  
Transcription Factor ◽  
Candida Albicans ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Wild Type ◽  
Content Type ◽  
Hypha Formation ◽  
Physical Presence ◽  
J774 Cells ◽  
Low Levels

ABSTRACTThe interaction ofCandida albicanswith macrophages induces the production of interleukin 1β (IL-1β) through inflammasome activation in a process that is required for host survival.C. albicanshypha formation has been linked to IL-1β production, but the question of whether hyphae are sufficient to trigger IL-1β production has not been examined directly. To address this question, aC. albicanslibrary of 165 transcription factor deletion mutants was screened for strains with altered IL-1β production by lipopolysaccharide (LPS)-primed J774 cells, a murine macrophage-like cell line. Eight mutants with decreased and two mutants with increased IL-1β secretion were identified. In addition, 12 mutants with previously identified morphology deficits were found to induce IL-1β secretion to levels similar to those of the wild type. Examination of the morphology of both low and normal IL-1β-inducing mutants in macrophages revealed that two mutants (upc2Δ/upc2Δ andahr1Δ/Δ mutants) were indistinguishable from the wild type with respect to morphology yet induced low levels of IL-1β; conversely, thendt80Δ/Δ mutant was deficient for hypha formation but induced levels of IL-1β similar to those of the wild type. Transcription factor mutants deficient for IL-1β secretion also caused markedly lower levels of macrophage lysis. Similarly, the ability of a mutant to cause macrophage lysis was independent of its ability to form hyphae. Taken together, our observations indicate that the physical formation of hyphae is not sufficient to trigger IL-1β secretion or macrophage lysis and suggest that other mechanisms, such as pyroptosis, a caspase-1-dependent response to intracellular pathogens, may play a role in the interaction of macrophages withC. albicans.IMPORTANCEThe ability ofCandida albicansto transition from yeast to filamentous cells plays an important and complex role in pathogenesis. Recent results from a number of investigators indicate that the host responds to yeast and hyphalC. albicansdifferently. For example, aC. albicansmutant unable to form hyphae also fails to induce interleukin 1β (IL-1β) secretion from macrophages. We have identifiedC. albicanstranscription factor mutants that have decreased IL-1β secretion but retain the ability to form hyphae in response to macrophages. In addition, these mutants cause significantly less macrophage lysis. These observations indicate that the physical presence of the hyphal structure in the macrophage is not sufficient to trigger IL-1β secretion nor does it cause physical lysis of the cell. Our data indicate that characteristics of hyphae separate from its physical morphology are responsible for triggering the release of IL-1β release and causing macrophage lysis. Since these observations are inconsistent with some current models, alternative mechanisms for the interaction ofC. albicanswith macrophages must be considered.

scholarly journals Implication of the NLRP3 Inflammasome in Bovine Age-Related Sarcopenia

2021 ◽  
Vol 22 (7) ◽  
pp. 3609
Author(s):  
Davide De Biase ◽  
Giuseppe Piegari ◽  
Francesco Prisco ◽  
Ilaria Cimmino ◽  
Ilaria d’Aquino ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Nlrp3 Inflammasome ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Interleukin 18 ◽  
Necrosis Factor Alpha ◽  
Age Related ◽  
Factor Alpha ◽  
Bovine Skeletal Muscle ◽  
First Time

Sarcopenia is defined as the age-related loss of skeletal muscle mass, quality, and strength. The pathophysiological mechanisms underlying sarcopenia are still not completely understood. The aim of this work was to evaluate, for the first time, the expression of NLRP3 inflammasome in bovine skeletal muscle in order to investigate the hypothesis that inflammasome activation may trigger and sustain a pro-inflammatory environment leading to sarcopenia. Samples of skeletal muscle were collected from 60 cattle belonging to three age-based groups. Morphologic, immunohistochemical and molecular analysis were performed to assess the presence of age-related pathologic changes and chronic inflammation, the expression of NLRP3 inflammasome and to determine the levels of interleukin-1β, interleukin-18 and tumor necrosis factor alpha in muscle tissue. Our results revealed the presence of morphologic sarcopenia hallmark, chronic lymphocytic inflammation and a type II fibers-selective NLRP3 expression associated to a significant decreased number of immunolabeled-fibers in aged animals. Moreover, we found a statistically significant age-related increase of pro-inflammatory cytokines such as interleukin-1β and interleukin-18 suggesting the activation of NLRP3 inflammasome. Taken together, our data suggest that NLRP3 inflammasome components may be normally expressed in skeletal muscle, but its priming and activation during aging may contribute to enhance a pro-inflammatory environment altering normal muscular anabolism and metabolism.

Microcystin-LR Induces NLRP3 Inflammasome Activation via FOXO1 Phosphorylation, Resulting in Interleukin-1β Secretion and Pyroptosis in Hepatocytes

2020 ◽  
Author(s):  
Yali Zhang ◽  
Peipei Zhu ◽  
Xiaofeng Wu ◽  
Tianli Yuan ◽  
Zhangyao Su ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Inflammatory Injury ◽  
Nlrp3 Inflammasome Activation ◽  
Phosphatase 2A ◽  
Related Proteins

Abstract Microcystin-LR (MC-LR), the most common and toxic microcystin (MC) present in freshwater, poses a substantial threat to human health, especially hepatotoxicity. Recent evidence reveals that the NLRP3 inflammasome plays an important role in liver injury by activating caspase-1 to promote interleukin-1β (IL-1β) secretion. In this study, we investigated the possible role of NLRP3 inflammasome activation in MC-LR-induced mouse liver inflammatory injury. We found that MC-LR administered to mice by oral gavage mainly accumulated in liver and induced the activation of the NLRP3 inflammasome and production of mature IL-1β. Additionally, we observed an increase in the levels of NLRP3 inflammasome-related proteins and the proportion of pyroptosis in MC-LR-treated AML-12 cells. We also found that inhibition of NLRP3 in mice attenuated MC-LR-induced IL-1β production, indicating an essential role for NLRP3 in MC-LR-induced liver inflammatory injury. In addition, we found that inhibition of FOXO1 by AKT-mediated hyperphosphorylation, due to protein phosphatase 2A (PP2A) inhibition, is required for MC-LR-induced expression of NLRP3. Taken together, our in vivo and in vitro findings suggest a model in which the NLRP3 inflammasome activation, a result of AKT-mediated hyperphosphorylation of FOXO1 through inhibition of PP2A, plays a key role in MC-LR–induced liver inflammatory injury via IL-1β secretion and pyroptotic cell death.

Citrobacter freundii Activation of NLRP3 Inflammasome via the Type VI Secretion System

2020 ◽  
Author(s):  
Liyun Liu ◽  
Liqiong Song ◽  
Rong Deng ◽  
Ruiting Lan ◽  
Wenjie Jin ◽  
...  
Keyword(s):  
Nlrp3 Inflammasome ◽  
Secretion System ◽  
Interleukin 1Β ◽  
Inflammasome Activation ◽  
Dependent Manner ◽  
Citrobacter Freundii ◽  
Type Vi Secretion System ◽  
Type Vi Secretion ◽  
Tract Infections

Abstract Citrobacter freundii is a significant cause of human infections, responsible for food poisoning, diarrhea, and urinary tract infections. We previously identified a highly cytotoxic and adhesive C. freundii strain CF74 expressing a type VI secretion system (T6SS). In this study, we showed that in mice-derived macrophages, C. freundii CF74 activated the Nucleotide Oligomerization Domain -Like Receptor Family, Pyrin Domain Containing 3(NLRP3) inflammasomes in a T6SS-dependent manner. The C. freundii T6SS activated the inflammasomes mainly through caspase 1 and mediated pyroptosis of macrophages by releasing the cleaved gasdermin-N domain. The CF74 T6SS was required for flagellin-induced interleukin 1β release by macrophages. We further show that the T6SS tail component and effector, hemolysin co-regulation protein-2 (Hcp-2), was necessary and sufficient to trigger NLRP3 inflammasome activation. In vivo, the T6SS played a key role in mediating interleukin 1β secretion and the survival of mice during C. freundii infection in mice. These findings provide novel insights into the role of T6SS in the pathogenesis of C. freundii.

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